Is MTPAP p.Pro59Ser (c.175C>T) pathogenic?

MTPAP p.Pro59Ser (c.175C>T) is classified Uncertain significance in MTPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely benign (0.0881); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MTPAP p.Pro59Ser (c.175C>T)?

MTPAP p.Pro59Ser (c.175C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTPAP p.Pro59Ser (c.175C>T) in the general population?

MTPAP p.Pro59Ser (c.175C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MTPAP p.Pro59Ser (c.175C>T)?

AlphaMissense predicts likely benign (score 0.0881) — an in-silico prediction, not a clinical call.

MTPAP p.Pro59Ser

c.175C>T · rs2538469642 · VCV2558848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0881 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0881	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -5.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.7, phastCons 0.12
Regional constraint	o/e 1.12	unconstrained · MANE · 7,745 bp · p 0.2 · regional, not allelic
Overall
CADD	7.694	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MTPAP
Protein: p.Pro59Ser
Coding: c.175C>T
MANE Select: NM_018109
dbSNP: rs2538469642
Type: single nucleotide variant
Location: chr10:30341623 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 83.16 · 1 PDB

Full MTPAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTPAP p.Ala141Thr Uncertain significance ★★ ⚠ same condition
MTPAP p.Arg160Trp Uncertain significance ★★ ⚠ same condition
MTPAP p.Arg171Cys Uncertain significance ★★ ⚠ same condition
MTPAP p.Arg461Gln Uncertain significance ★★ ⚠ same condition
MTPAP p.Asn167Ser Uncertain significance ★★ ⚠ same condition
MTPAP p.Asn522Ser Uncertain significance ★★ ⚠ same condition
MTPAP p.Asn556Thr Uncertain significance ★★ ⚠ same condition
MTPAP p.Cys119Tyr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mtpap-p-pro59ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown